Vasospasm induced myocardial ischaemia secondary to sumatriptan use

Abstract

Certain medications have been implicated in causing acute myocardial infarctions (AMI). Sumatriptan, a medication usually prescribed for acute migraine and cluster headaches has been documented as potentially causing coronary vasospasm, thereby leading to MI. This is usually seen in patients with strong risk factors for coronary artery disease (CAD) or in those with established CAD. Most cases thus far have been reported in patients using the subcutaneous preparation of sumatriptan. Here, we present a case of a patient without prior risk factors for CAD and angiographically unremarkable coronary arteries who presented with evidence of an AMI after oral sumatriptan use for migraines.

Background

Acute myocardial infarctions (AMIs) occur as a result of compromised blood flow and oxygen to heart muscles. Most AMIs are caused by coronary artery disease (CAD).¹ Certain drugs can also lead to MI; such drugs include cocaine, which is well known to cause coronary vasospasm, non-steroidal anti-inflammatory drugs and triptans. It is unclear to what extent sumatriptans impede myocardial perfusion and cause AMIs. Indeed, the British National Formulary, published by the British Medical Association and Royal Pharmaceutical Society, informs prescribers that despite its unknown frequency, AMIs are a possible adverse effect following sumatriptan use.² By 1990, almost 5000 patients had been enrolled into clinical trials investigating the efficacy of sumatriptan against placebos. Chest pain was observed in 3% of patients receiving sumatriptan, and one case of myocardial ischaemia was identified in a patient taking sumatriptan.³ A study by O’Quinn et al⁴ investigated the safety of sumatriptan use in patients from 16 to 82 years of age. The study showed that of the 185 579 migraine attacks treated with sumatriptans, three MIs, six episodes of angina and four episodes of arrhythmias were reported. Ottervanger et al⁵ analysed drug-induced chest pain over a 20-year period. After excluding cases in which a causal relationship was unlikely, poorly documented or reported overdose the group found a total of 130 reports of chest pain and 53 reports of drug-inducted MI. Of these cases, 33 reports of chest pain and four of MIs were attributed to sumatriptan use. Taken together, these studies highlight that cases of cardiovascular risks following sumatriptan use are increasing over the years and remain a real threat. Here, we present a case of a patient, without prior cardiovascular risk factors and unremarkable angiograms, diagnosed with AMI as a result of sumatriptan-induced coronary artery vasospasm.

Case presentation

A 55-year-old university professor presented to the emergency department (ED) with a dull aching pain around the epigastrium and lower sternal areas. He had a background history of hiatus hernia, asthma, two previous deep venous thrombosis and migraine headaches.

The patient developed a headache while watching the results of the 2017 British general elections around 04:00 and took two sumatriptan 50 mg tablets before going to sleep. He woke up around 06:30 with the dull chest ache described as an ‘internal pressure’ and ranked it as a 2/10 in terms of pain severity. The pain radiated to his left hand and wrist. There was associated diaphoresis. The pain lasted 30 min in duration. There was no accompanying shortness of breath.

On further questioning it was determined he had no prior risk factors for CAD. He was apyrexial, and his vitals signs were as follows:

• Blood pressure: 145/105 mmHg.

• Pulse: 72 beats per minute.

• Respiratory rate: 17 breaths per minute.

• Oxygen saturation: 98% on room air.

• Consequently, he was deemed to have a National Early Warning Score of 0.

• Cardiovascular and respiratory examinations were unremarkable, and blood was taken.

Investigations

The initial workup for the patient consisted of a series of blood tests. Full blood count did not show any evidence of infection, and C reactive protein did not demonstrate any evidence of inflammation. The first troponin-I levels were elevated at 245 ng/L. Repeat troponin-I levels were markedly raised at 2666 ng/L. The renal profile showed that all electrolytes were within normal parameter, and D-dimer levels were found to be less than 150 ng/mL. Random glucose was 5.7 mmol/L, and liver functions tests were not deranged. Total cholesterol levels were found to be 5.50, and triglyceride levels were 1.60. Chest X-ray did not show any acute pathology.

Initial ECG, during which the chest pain had diminished, was largely unremarkable except small T-wave inversions in V4–V6 (figure 1). The patient did not have prior ECGs for comparison. Following these results, however, the patient was thought to have a non-ST elevated MI and subsequently moved to the coronary care unit. A repeat ECG was conducted 2 hours after admission which showed deepening T-waves across V2–V5 (figure 2). From day 2 onwards after admission, the ECG showed further prominent T-wave inversions in leads I, II, III, aVL and aVF (figure 3).

Figure 1.

ECG on presentation.

Figure 2.

ECG 2 hours after presentation; deepening T-waves in V2–V5.

Figure 3.

ECG on day 3 of admission; prominent T-wave inversions in leads I, II III, aVL and aVF.

While the patient did not have any subsequent chest pain, further imaging and scans were conducted. During day 3 of the patient’s admission, an echocardiogram was performed. Echocardiogram showed that the basal-inferior and infero-lateral wall segments were hypokinetic, and the left ventricular systolic function was not impaired (ejection fraction >55%). Furthermore, valvular abnormalities and atrial dysfunction were not detected.

The patient then also underwent a coronary angiography the same day, prior to which two puffs of glyceryl trinitrate spray was administered. The angiogram showed a dominant right coronary artery and did not demonstrate any pathology within the coronary vessels (figure 4). Subsequently, it was deemed that this patient did not have prior risk factors for CAD, but rather his AMI was a result of coronary vasospasm induced by sumatriptan.

Figure 4.

Angiogram showing patent coronary arteries.

Differential diagnosis

Chest pain is a common presenting complaint in ED. Indeed in our case, there are several differentials which can be best categorised by organ system. Table 1 shows the potential differential diagnosis, along with its rationale and excluding criteria for our patient, who reported pain around the epigastrium and substernal region.

Table 1.

Potential differential diagnosis prior to confirmation of AMI by ECG changes and elevated troponin levels

Organ system	Differentials	Rationale	Excluding factor(s)
Respiratory	Pulmonary embolism	Previous history of DVT	No evidence of hypoxia D-dimer not elevated No evidence of tachycardia
	Pneumonia	Associated diaphoresis and headache may indicate infectious and inflammatory process	Apyrexial White cells not elevated Unremarkable chest X-ray
	Asthma	Prior medical history of asthma	No evidence of hypoxia No evidence of wheeze on physical examination
Cardiac	Angina	Cardiac symptoms suggestive of angina	Duration of history not suggestive of angina
	MI	Typical presentation of chest pain, radiating down to arm, associated with diaphoresis	No risk factors for CAD
	Arrythmia	Patient awake late night—may have taken caffeine to stay awake	No evidence suggestive of arrythmia found on ECG
Gastrointestinal	GORD	Prior medical history of hiatus hernia	Character and pain radiation not suggestive of GORD
	Peptic ulcer	Pain in epigastrum is typical of peptic ulcer	Character and pain radiation not suggestive of peptic ulcers
Musculoskeletal	Costochondritis	Associated diaphoresis may indicated underlying infection which could precipitate costochondritis	No tenderness over the ribs No evidence of underlying infection on full blood count
Psychological	Anxiety	Pain brought on after watching the national general election University professor may have work related stress	No previous history of anxiety

AMI, acute myocardial infarction; CAD, coronary artery disease; DVT, deep venous thrombosis; GORD, gastro-oesophageal reflux disease; MI, myocardial infarction.

Treatment

Soon after the presentation, when the troponin-I levels and ECG changes were known, the patient received dual antiplatelet therapy (DAPT), and fondaparinux. Once that patient’s cause of the AMI was known following angiography, the patient was put on DAPT, ACE inhibitors (ACEi) and beta-blockers for 6 months.

Outcome and follow-up

The patient was reviewed in the cardiology clinic 4 months later. He was completely pain-free after his admission. He had a repeat echocardiogram which showed good left ventricular systolic function. There were no regional wall motion abnormalities. A repeat ECG showed a sinus rhythm with a first degree atrioventricular (AV) block. There were T-wave inversions only in lead III. His aspirin was discontinued as he reported dyspepsia. He was continued on rivaroxaban and subsequently discharged from the clinic.

Discussion

Sumatriptan is among the most extensively studied migraine medications. Sumatriptan is selective agonists of 5-hydroxytryptamine, (5-HT₁) receptors.⁶ It is used in the abortive treatment of migraines⁴. Sumatriptan is thought to act by mediating the inhibition of neuroinflammatory peptide release, thereby causing cerebral vasoconstriction.⁷ Sumatriptan has a half-life (t_1/2) of approximately 90 min.⁸ While it was previously thought that most vascular beds in the body outside of the cranial circulation contained only 5-HT₂ receptors and were therefore not susceptible to 5-HT₁ receptor-mediated vasoconstriction. Studies have, however, further suggested that the coronary circulatory system does contain 5-HT_1b receptors.⁹ Therefore it is now clear that their presynaptic effects of mediating the inhibition of neuropeptide release might also reflect a primary site of action. Some studies have suggested that atheromatous coronary arteries may be more prone to 5-HT₁ receptor-medicated vasoconstriction.¹⁰ Coronary artery vasospasm is defined by intense and reversible vasoconstriction of a coronary artery branch which results in sudden subtotal or total occlusion.¹¹ This phenomenon in itself is a rare occurrence with an estimated prevalence between 1% and 1.5% among angina admissions.¹²

Postmarketing data have evaluated the potential cardiovascular risk of sumatriptan. Thirty-nine cardiovascular deaths were reported between 1991 and 1996. This was in those patients who received sumatriptan within 24 hours of death. The occurrence of angina, arrhythmias and MI was <1 per million. This data, therefore, suggests that serious cardiovascular events are quite rare with sumatriptan use. Some case reports of patients experiencing cardiovascular events MI, unstable angina, arrhythmias and even cardiac arrest in close temporal relation with the use of sumatriptan have been made.^13–15 This has led to some recommending that a cardiac evaluation be done on all patients at risk of unrecognised CAD before commencing use of triptans.

The Japanese Coronary Spasm Association has proposed a prognostic prediction score for coronary vasospasm.¹⁶ Prognostic factors and their respective score include; out of hospital cardiac arrest (4) smoking (2), organic coronary stenosis (2), multivessel spasm (2), angina at rest (2), beta-blockers (1), ST-segment elevation(1).¹⁶ Based on these criteria, our patient scored 2 points for angina at rest, putting him at relatively low risk of an adverse outcome. Indeed this is reflected by the fact that the patient was discharged from the clinic relatively swiftly. However, it is important to consider that patients who score higher on this system and are also taking sumatriptan may have a higher risk of having an adverse outcome. Weder et al¹⁷ reported a case of a 67-year-old woman who was diagnosed with AMI following triptan used. Indeed this patient had cardiac risk factors including hypertension. The group argued that triptans should not be prescribed in patients older than 65 years of age with underlying coronary risk factors. However, it must be noted that in this case, the patient was receiving naratriptan rather than sumatriptan. Main and colleagues¹⁸ further reported a case of a 48-year-old woman on a background of type 2 diabetes and smoking history who suffered from migraine and received 6 mg of sumatriptan subcutaneously. The patient suffered chest tightness and had cardiac arrest within 10 min of administration. Similarly, Mueller et al¹⁹ described a case of 56-year-old woman who was an ex-smoker suffering from an AMI following subcutaneous sumatriptan use. Her cardiovascular evaluation was unremarkable, as was her angiogram. She did not have a history of any other significant coronary risk factors including diabetes mellitus, hyperlipidemia and hypertension. In several of these cases, the sumatriptan was delivered subcutaneously. Here were present a case of coronary artery vasospasm, causing AMI secondary to oral sumatriptan use. We advocate that careful evaluation is conducted with regards to patients’ coronary risk factors prior to prescribing sumatriptan. Moreover, we recommend that patients are accurately informed of the possibility of MI when being prescribed these medications and advised to seek medical attention should they experience any chest tightness.

Learning points.

• Although rare, sumatriptans induced coronary vasospasm remains a real threat for acute myocardial infarction.

• Physicians ought to advise patients to seek medical attention if they experience chest pain following sumatriptan use or any similar medications which can induce coronary vasospasm.

• It is important to consider different mechanisms by which myocardial infarction can occur, especially in patient with without risk factors for coronary artery disease.